The recommended dose (RD) will be the immediate lower DL below the MTD (maximum tolerated dose)with less than 1/3 of the first 6 evaluable patients experiencing DLT (dose limiting toxicity)during the induction, provided the RD is ≥ dose level 2. If the RD is determined at dose level 1, no further expansion will be done, and the study will be terminated.

The recommended dose (RD) will be the immediate lower DL below the MTD (maximum tolerated dose)with less than 1/3 of the first 12 evaluable patients experiencing DLT (dose limiting toxicity)during the induction, provided the RD is ≥ dose level 2. If the RD is determined at dose level 1, no further expansion will be done, and the study will be terminated.

Antileukemic activity [ Time Frame: After induction/reinduction and every 4 weeks after treatment discontinuation; up to 30 months ] [ Designated as safety issue: No ]

Activity will be defined according to the International Working Group (IWG) criteria.

Pharmacogenomic (PGx) profile of PM01183 in patients with advanced acute leukemia. [ Time Frame: Between day -24 to day 1 ] [ Designated as safety issue: No ]

Identification of potential biomarkers of response to PM01183

Pharmacokinetics (PK) of PM01183 in patients with advanced acute leukemia [ Time Frame: Days 1 to 8 of induction and day 1 of next phase ] [ Designated as safety issue: No ]

The PK will be elucidated using standard non-compartmental methods. The following parameters will be calculated: maximum drug concentration (Cmax), area under the curve (AUC), volume of distribution based on the terminal half-life (Vz), volume of distribution at steady state (Vss), clearance (CL) and half-life (t1/2)

Original Secondary Outcome Measures ICMJE

Same as current

Current Other Outcome Measures ICMJE

Not Provided

Original Other Outcome Measures ICMJE

Not Provided

Descriptive Information

Brief Title ICMJE

Clinical Study of PM01183 in Patients With Acute Leukemia or Relapsed/Refractory Myelodysplastic Syndrome

Phase I Study of PM01183 in Patients with Advanced Acute Leukemia to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183.

Detailed Description

Open-Label, Dose-Escalating, Clinical and Pharmacokinetic Phase I Study of PM01183 in Patients with Advanced Acute Leukemia to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 administered as 1-hour intravenous (i.v.) infusion on three consecutive days (Days 1-3) to patients with advanced acute leukemia and to assess the safety profile and tolerability, to obtain preliminary information on the efficacy and to characterize the pharmacokinetics (PK) and pharmacogenomic (PGx) profile of PM01183.

Study Type ICMJE

Interventional

Study Phase

Phase 1

Study Design ICMJE

Endpoint Classification: Safety StudyIntervention Model: Single Group AssignmentMasking: Open Label

Condition ICMJE

Acute Leukemia

Intervention ICMJE

Drug: PM01183 1 mg Powder for concentrate for solution for infusion and PM01183 4 mg Powder for concentrate for solution for infusion

PM01183 Drug Product will be provided as a lyophilized powder for concentrate for solution for infusion with a strength of 1.0 mg/vial and 4.0 mg/vial.

Before use, the vials will be reconstituted with 2 ml or 8 ml of sterile water for injection to give a solution containing 0.5 mg/ml of PM01183.

Study Arm (s)

Experimental: Arm 1

PM01183 will be administered i.v. as a 1-hour infusion through a pump device at escalating doses according to the respective dose level, on Days 1 and 8 of each treatment phase.

Intervention: Drug: PM01183 1 mg Powder for concentrate for solution for infusion and PM01183 4 mg Powder for concentrate for solution for infusion

Publications *

Not Provided

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Completed

Enrollment ICMJE

45

Completion Date

July 2015

Primary Completion Date

July 2015 (final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Voluntarily signed and dated written informed consent

Age ≥ 18 years.

Patients must have a previous cytological or histological diagnosis of:

Relapsed or primary refractory non-M3 acute myeloid leukemia (AML) by the World Health Organization (WHO) criteria (irrespective of the number of prior regimens), either de novo or secondary [i.e., secondary to myelodysplastic syndromes (MDS), myeloproliferative neoplasms or previous chemotherapy for another condition].

Untreated AML in patients ≥ 65 years of age, if patients are not candidates for standard induction chemotherapy or have poor risk AML (i.e., secondary AML or AML with adverse cytogenetics or complex karyotype).

Pregnant or lactating women; men and women of reproductive potential who are not using effective contraceptive methods throughout the treatment period and for six months after discontinuation of treatment.

Patients who plan to undergo allogeneic BM transplantation within four weeks.

Other relevant diseases or adverse clinical conditions:

History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.

Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.

Hematopoietic allogeneic stem cell transplantation within the last four months and/or active graft versus host disease, or prior autologous transplantation within the last four weeks.

Patients known to be human immunodeficiency virus (HIV) positive.

Cytotoxic chemotherapy within the last two weeks; radiation therapy within the last two weeks; biologic agents, including hematopoietic growth factors, within the last week; hydroxyurea, imatinib, corticosteroids and arsenic trioxide should be discontinued at least 24 hours prior to first study drug administration.

Treatment with any investigational product in the ≤ 5 half-lives period prior to inclusion in the study, or 30 days after therapy (in case of unknown half-life), unless evidence of rapid proliferating disease and upon discussion with the Sponsor.

Known hypersensitivity to any of the components of the drug product (DP).

Gender

Both

Ages

18 Years and older (Adult, Senior)

Accepts Healthy Volunteers

No

Contacts ICMJE

Contact information is only displayed when the study is recruiting subjects